The emphasis in this laboratory has been on two general areas of investigation: 1) mechanisms of control of cholesterol synthesis, and 2) the mechanisms of bile acid absorption. In the present research grant application 4 general categories of experiments are outlined: 1) The first set of studies is designed to investigate the adaptive mechanisms that occur in the rat after resection of the proximal or distal small intestine. In these studies, the changes in the rate of endogenous cholesterol synthesis in liver and gut will be measured as well as changes in net bile acid excretion and net neutral sterol excretion. 2) The second set of investigations is designed to evaluate the inhibitory capacity of various lipoprotein fractions in the rat and in man. An in vivo rat assay system is described in which the capacity of cholesterol carried in each of the major lipoprotein fractions to inhibit hepatic sterol synthesis can be determined. 3) The third series of investigations is designed to isolate the membrane carrier component of ileum responsible for the active transport of bile acid. A detailed kinetic analysis of the active transport of bile acid across the entire small bowel and ileum has been worked out in this laboratory. Experiments will be undertaken in isolated brush border preparations, in disrupted microvillus membranes, and ultimately in fragments of the isolated brush border membranes. It is hoped that these studies will lead ultimately to isolation of a specific protein or lipoprotein from the ileal brush border that participates in active bile acid transport. 4) The final series of experiments involves elucidation of the mechanisms of bile acid transport across the colon. Using an in vivo animal preparation, the permeation constants for various bile acids will be measured across the colon of the rat.